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Title: | Molecular genetic heterogeneity in undifferentiated endometrial carcinomas |
Author: | Rosa Rosa, Juan Manuel Leskela, Susanna Cristóbal Lana, Eva Santón, Almudena López García, Ma. Ángeles Muñoz, Gloria Pérez Mies, Belén Biscuola, Michele Prat, Jaime Oliva, Esther Soslow, Robert A. Matias-Guiu, Xavier Palacios, José |
Keywords: | Càncer d'endometri Genètica molecular Endometrial cancer Molecular genetics |
Issue Date: | 1-Nov-2016 |
Publisher: | Nature Publishing |
Abstract: | Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumors, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well-differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing. Whole-exome sequencing of the endometrioid and undifferentiated components, as well as normal myometrium, was also carried out in one case. According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: (a) hypermutated tumors with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); (b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); (c) high copy number alterations (copy-number high) tumors group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%); and (d) low copy number alterations (copy-number low) tumors with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%). Two of the latter cases, however, also had TP53 mutations and higher number of alterations detected by FISH and could have progressed to a copy-number high phenotype. Most dedifferentiated carcinomas belonged to the hypermutated group, whereas pure undifferentiated carcinomas shared molecular genetic alterations with copy-number low or copy-number high tumors. These results indicate that undifferentiated and dedifferentiated endometrial carcinomas are molecularly heterogeneous tumors, which may have prognostic value. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1038/modpathol.2016.132 |
It is part of: | Modern Pathology, 2016, vol. 29, num. 11, p. 1390-1398 |
URI: | http://hdl.handle.net/2445/125366 |
Related resource: | https://doi.org/b10.1038/modpathol.2016.132 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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